Aberrant epigenetic changes are a driving force in many human cancers. The focus of our lab is centred on understanding how epigenetics impacts gene regulation so that this information can potentially be used to develop new therapeutic strategies.
Children with mutations in the Mixed Lineage Leukaemia (MLL) gene do not respond well to conventional therapies and thus have very poor survival rates. This is likely due to the fact that MLL is a master regulator that modifies the “epigenetic” information content of a cell. Epigenetic information is not stored in the DNA itself, but in specialized proteins called histones. Histones can have chemical modifications or “marks” attached to them that can code for gene activation or repression. It is becoming clear not only that aberrant epigenetic changes are common in many human diseases such as leukaemia, but that these changes by their very nature are reversible. A great number of epigenetic proteins that have been implicated in human disease have also turned out to be enzymes that are involved in adding (“writing”), removing (“erasing”) or interpreting (“reading”) histone marks. Effective therapies are likely to require a cocktail of different inhibitors and will therefore depend on a clear understanding of how multiple epigenetic proteins cooperate in disease progression. The focus of our lab is centred on understanding how epigenetics impacts gene activation and repression in normal and leukaemic cells. The end goal will be to use this information to identify potentially novel drug combinations for use in leukaemia.